Microspheres with encapsulated or covalently bonded biologically-active agent allow provision of an injectable suspension as a substitute for surgical implantation and facilitate administration of multiple drugs in a single injection. These microspheres provide an initial burst to reach a therapeutic concentration followed by a zero-order release of drug to maintain the therapeutic level by compensating for metabolic loss. The microspheres thus provide a sustained release therapeutic concentration.
Microspheres of biodegradable polyesters from D,L-lactide/glycolide and microspheres of biodegradable polyesters from ε-caprolactone have received attention for controlling release in the body of pharmaceutical agents and macromolecules. However, these polyesters are relatively hydrophobic and a more hydrophilic surface is desirable on an injectable microsphere to increase effective lifetime in the circulatory system and to reduce the occurrence of an inflammatory response. Hydrophilic characteristics have been achieved by surface modification of the polyester microspheres with hydrophilic polymers. Polyester microspheres with more hydrophilic surfaces have not heretofore been obtained without relying on chemical attachment or physical absorption of hydrophilic polymers.